title: Is the oxidant/antioxidant status altered in CADASIL patients?
abstract: The altered aggregation of proteins in non-native conformation is associated with endoplasmic reticulum derangements, mitochondrial dysfunction and excessive production of reactive oxygen species. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary systemic vasculopathy, caused by NOTCH3 mutations within the receptor extracellular domain, that lead to abnormal accumulation of the mutated protein in the vascular wall. NOTCH3 misfolding could cause free radicals increase also in CADASIL. Aim of the study was to verify whether CADASIL patients have increased oxidative stress compared to unrelated healthy controls. We enrolled 15 CADASIL patients and 16 gender- and age-matched healthy controls with comparable cardiovascular risk factor. Blood and plasma reduced and total aminothiols (homocysteine, cysteine, glutathione, cysteinylglycine) were measured by HPLC and plasma 3-nitrotyrosine by ELISA. Only plasma reduced cysteine (Pr-Cys) and blood reduced glutathione (Br-GSH) concentrations differed between groups: in CADASIL patients Br-GSH levels were higher (p = 0.019) and Pr-Cys lower (p = 0.010) than in controls. No correlation was found between Br-GSH and Pr-Cys either in CADASIL patients (rho 0.25, P = 0.36) or in controls (rho -0.15, P = 0.44). Conversely, 3-nitrotyrosine values were similar in CADASIL and healthy subjects (p = 0.82). The high levels of antioxidant molecules and low levels of oxidant mediators found in our CADASIL population might either be expression of an effective protective action against free radical formation at an early stage of clinical symptoms or they could suggest that oxidative stress is not directly involved in the pathogenesis of CADASIL.
authors.affiliation: Community Networking Resources Institute of Clinical Physiology, Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Milan, Italy. jonica.campolo@ospedaleniguarda.it
authors.forename: Jonica
authors.initials: J
authors.lastname: Campolo
authors.forename: Renata
authors.initials: R
authors.lastname: De Maria
authors.forename: Caterina
authors.initials: C
authors.lastname: Mariotti
authors.forename: Chiara
authors.initials: C
authors.lastname: Tomasello
authors.forename: Marina
authors.initials: M
authors.lastname: Parolini
authors.forename: Marina
authors.initials: M
authors.lastname: Frontali
authors.forename: Domenico
authors.initials: D
authors.lastname: Inzitari
authors.forename: Raffaella
authors.initials: R
authors.lastname: Valenti
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
authors.forename: Oberdan
authors.initials: O
authors.lastname: Parodi
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D046589:CADASIL / Q000097:blood*; D016022:Case-Control Studies; D003545:Cysteine / Q000097:blood; D004151:Dipeptides / Q000097:blood; D005260:Female; D005978:Glutathione / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D016877:Oxidants / Q000097:blood; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D000975:Antioxidants; D004151:Dipeptides; D016877:Oxidants; D006710:Homocysteine; C002744:3-nitrotyrosine; C028505:cysteinylglycine; D014443:Tyrosine; D005978:Glutathione; D003545:Cysteine